Abstract/Summary (Animal Models Core?Core 3) Animal models of cystic fibrosis (CF) are critical for the development of effective gene and molecular therapies. In particular, animal models that reproduce the clinical manifestations of CF are necessary for elucidating the pathophysiologically relevant cellular targets for gene therapy, and aid in the development and testing of gene vector technologies for therapeutic efficacy. The Animal Models Core has provided support to investigators who use animal models to study the pathogenesis of CF and who develop gene and other molecular therapies for CF. Specifically, it provides centralized production, care, breeding, genotyping, and quality control of CF mouse and ferret models used by investigators in the Center. Additionally, the Core has served as a conduit for dissemination of CF pig tissue resources from other funded programs in the Carver College of Medicine. However, because of the cost of maintaining CF pigs, the Core has not established its own colony and relies on the established company Exemplar Genetics for distribution outside the University of Iowa (UI). The Core also assists in managing BL2 containment and compliance in animal experiments with recombinant viruses by investigators of the Center. Technicians within the Core facilitate the more technically challenging aspects of studies in CF animal models, such as viral vector administration, bacterial challenge, the dosing and testing of antimicroblials and anti-inflammatory coupounds, and tissue harvesting. The Core also provides CF and non- CF tracheobronchial xenograft models at the disposal of Center investigators. Tracheobronchial xenograft models are generated using either CF/non-CF primary airway cells from human, pig, or ferret, or using native airway implants from CF/non-CF pigs and ferrets. Recently, the Core was instrumental in the creation of gut- corrected CFTR-deficient ferrets. In this context, the Core has played a major role in developing technologies for cloning ferrets by nuclear transfer and gene targeting techlogies that use fibroblasts as the source of donor nuclei. The generation of larger CF animal models (pig and ferret) has had a significant impact on services provided by the Animal Models Core. During the last 5 years the Core greatly increased it dissemination of CF ferret tissue resources to investigators, having served 14 investigators at UI and 29 investigators outside UI. This has enabled cost-effective broad use of the model, and leverages costs needed to establish a large colony and rear CF ferrets. Although this Core directs the majority of its efforts toward CF gene therapy and CF pathophysiology, it also provides extensive support for the research on lung biology and CF-related diabetes. During the next funding period, the goals of the Core will be: 1. Genotyping of transgenic and knockout mice that are relevant to CF research. 2. Assisting in gene delivery to, and tissue harvesting from, animal models. 3. Rearing of CF ferrets that are used by multiple investigators inside and outside UI. 4. Generating human, pig, and ferret tracheobronchial xenograft models. 5. Harvesting and distributing CF ferret and pig tissues for use at UI. 6. Performing studies in the CF and non-CF ferrets for investigators at UI. 7. Distributing CF ferret resources and carrying out on-site studies in ferrets for investigators outside UI.